(±)-5-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole hydrochloride having the formula (I) following below is a synthetic α-2-adrenoreceptor agonist with sedative and analgesic properties
U.S. Pat. No. 4,544,664 discloses the leading multi-step process for preparing (±)-5-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride. The process starts with 2,3-dimethylmagnesium bromide, which is prepared from magnesium and 2,3-dimethylbromobenzene, while in a separate step this Grignard reagent is added to 4-imidazolecarboxylic acid methyl ester. The intermediate is hydrogenated in the presence of a palladium on carbon catalyst in hydrochloric acid.
GB 2069481 discloses the preparation of 5-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride via the intermediate 4-[(2′,3′-dimethylphenyl)-ethyl]-N-acetylimidazole or 4-[(2′,3′-dimethylphenyl)-ethyl]-N-benzylimidazole. In the processes described therein acetyl and benzyl groups are used as protecting groups of the intermediate products for increasing product yield.
In a further process described in this patent N-(trimethylsilyl)imidazole is used as a starting material, which is reacted with titanium tetrachloride in dry chloroform. In this case as protecting group a trimethylsilyl group is used. The use of a benzyl group as a protecting group is also mentioned therein.
The main disadvantage of the methods described in the above prior art documents is that medetomidine is obtained in low yields.